Early origin of sweet perception in the songbird radiation.

Early events in the evolutionary history of a clade can shape the sensory systems of descendant lineages. Although the avian ancestor may not have had a sweet receptor, the widespread incidence of nectar-feeding birds suggests multiple acquisitions of sugar detection. In this study, we identify a single early sensory shift of the umami receptor (the T1R1-T1R3 heterodimer) that conferred sweet-sensing abilities in songbirds, a large evolutionary radiation containing nearly half of all living birds.

Involvement of inflammation in severe post-operative pain demonstrated by pre-surgical and post-surgical treatment with piroxicam and ketorolac.

Objectives: Post-operative pain is considered to involve inflammation caused by tissue injury. However, the mechanism and timing of the involvement of inflammation in the post-operative pain remain complicated because they can vary among different types of surgery. In this study a rat incision model was used to investigate how inflammation induced by cyclooxygenases (COXs) is involved in severe post-operative pain.

Discovery and stereoselective synthesis of the novel isochroman neurokinin-1 receptor antagonist 'CJ-17,493'.

A novel central nervous system (CNS) selective neurokinin-1 (NK(1)) receptor antagonist, (2S,3S)-3-[(1R)-6-methoxy-1-methyl-1-trifluoromethylisochroman-7-yl]-methylamino-2-phenylpiperidine 'CJ-17,493' (compound (+)-1), was synthesized stereoselectively using a kinetic resolution by lipase-PS as a key step. Compound (+)-1 displayed high and selective affinity (K(i)=0.2 nM) for the human NK(1) receptor in IM-9 cells, potent activity in the [Sar(9), Met(O(2))(11)]SP-induced gerbil tapping model (ED(50)=0.

Effect of prostanoid EP4 receptor antagonist, CJ-042,794, in rat models of pain and inflammation.

Recent study suggests that the proinflammatory and nociceptive effects of prostaglandin E(2) are mediated by prostanoid receptor subtype EP(4) and prostanoid EP(4) receptor may be a potential target for the treatment of inflammatory pain. Here we describe pharmacological characterization of a novel prostanoid EP(4) receptor antagonist, CJ-042,794 (4-{(1S)-1-[({5-chloro-2-[(4-fluorophenyl) oxy] phenyl} carbonyl) amino] ethyl} benzoic acid) in comparison with piroxicam (non-steroidal anti-inflammatory drug) or rofecoxib (cyclooxygenase-2 inhibitor). CJ-042,794 competitively antagonized cAMP accumulation with a pA(2) value of 8.

Mathematical analysis of involvement ratio between central and peripheral COX-2 in rat pain models with two types of COX-2 inhibitors with different distribution, celecoxib and CIAA.

The purpose of this study is to clarify involvement ratios between central and peripheral cyclooxygenase (COX)-2 in rat inflammatory pain models, by evaluating celecoxib and [6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid (CIAA) on carrageenan-induced mechanical and thermal hyperalgesia. Celecoxib and CIAA exhibited ID(30) values with 1.5 and 7.

Differential involvement of TRPV1 receptors at the central and peripheral nerves in CFA-induced mechanical and thermal hyperalgesia.

Transient receptor potential vanilloid 1 (TRPV1) antagonists are known to attenuate two typical symptoms of inflammatory hyperalgesia: thermal and mechanical. However, it is not clear whether the sites of participation of TRPV1 for each symptom are different. In this study, we clarified the difference between the site of TRPV1 involvement in both symptoms by analysing the anti-hyperalgesic activity of two kinds of TRPV1 antagonists given locally (i.

Pharmacological separation between peripheral and central functions of cyclooxygenase-2 with CIAA, a novel cyclooxygenase-2 inhibitor.

There are many reports concerning the physiological and pathological involvement of cyclooxygenase (COX)-2 in the central nervous system and peripheral tissue cells. Selective COX-2 inhibitors that mainly distribute peripherally have not been reported thus far. Therefore central and peripheral roles of COX-2 remain classified pharmacologically.

A tachykinin NK1 receptor antagonist attenuates the 4 beta-phorbol-12-myristate-13-acetate-induced nociceptive behaviour in the rat.

Antinociceptive effect of a tachykinin NK1 receptor antagonist ezlopitant [(2S,3S-cis)-2-(diphenylmethyl)-N-{(2-methoxy, 5-isopropylphenyl)methyl}-1-azabicyclo[2.2.2]octan-3-amine] was investigated in the 4beta-phorbol-12-myristate-13-acetate (PMA)-induced nociceptive test in the rat.